The European Commission has approved pembrolizumab, an anti-PD-1 therapy, for the first-line treatment of metastatic non-small cell lung cancer (NSCLC) in adults whose tumours have high PD-L1 expression (tumour proportion score [TPS] of 50 percent or more) with no EGFR or ALK positive tumour mutations.

In August 2016, pembrolizumab (2 mg/kg every three weeks) was approved in Europe for previously-treated patients with locally advanced or metastatic NSCLC whose tumours express PD-L1 (TPS of 1 percent or more) and who have received at least one prior chemotherapy regimen.

“The approval of pembrolizumab as a first treatment instead of chemotherapy for patients who express high levels of PD-L1 has the potential to transform the way metastatic non-small cell lung cancer is treated,” said Dr. Roy Baynes, senior vice president, head of clinical development, and chief medical officer, Merck Research Laboratories, who market pembrolizumab under the name of Keytruda. “We are committed to ensuring that patients in Europe – who are in need of new treatment options – are able to quickly gain access to pembrolizumab.”

The approval is based on phase 3 data which demonstrated superior overall survival (OS) and progression-free survival (PFS) with pembrolizumab compared to chemotherapy, the current standard of care for advanced NSCLC.

The approval allows marketing of pembrolizumab in all 28 EU member states plus Iceland, Lichtenstein and Norway, at the approved dose of 200 mg every three weeks until disease progression or unacceptable toxicity. 

The European Commission’s approval is based on data from KEYNOTE-024, a randomized, open-label, phase 3 study evaluating pembrolizumab monotherapy at a fixed dose of 200 mg compared to standard of care platinum-containing chemotherapy (pemetrexed carboplatin, pemetrexed cisplatin, gemcitabine cisplatin, gemcitabine carboplatin, or paclitaxel carboplatin) for the treatment of patients with both squamous and non-squamous metastatic NSCLC.

The study enrolled 305 patients who had not received prior systemic chemotherapy treatment for their metastatic disease and whose tumours had high PD-L1 expression with no EGFR or ALK aberrations.

The primary endpoint was PFS; additional efficacy outcome measures were OS and objective response rate (ORR).

In the study, pembrolizumab reduced the risk of disease progression or death by 50 percent compared to chemotherapy (HR, 0.50 [95% CI, 0.37, 0.68]; p<0.001).

The median PFS for pembrolizumab was 10.3 months (95% CI, 6.7-not reached) compared to 6.0 months for chemotherapy (95% CI, 4.2-6.2).

At six months and 12 months, respectively, 62 percent and 48 percent of patients treated with pembrolizumab were alive and had no disease progression compared to 50 percent and 15 percent of those receiving chemotherapy.

Additionally, pembrolizumab resulted in a 40 percent reduction in the risk of death compared to chemotherapy (HR, 0.60 [95% CI, 0.41, 0.89]; p=0.005); this finding includes the 66 patients (43.7%) on the chemotherapy arm who crossed over in-study to receive pembrolizumab once their cancer had progressed; median OS was not reached in either group.

The OS rate at six months and 12 months, respectively, was 80 percent and 70 percent in patients treated with pembrolizumab compared to 72 percent and 54 percent in those receiving chemotherapy.

Further, ORR was 45 percent for patients receiving pembrolizumab (pembrolizumab) (95% CI, 37-53), including six complete responses, compared to 28 percent with chemotherapy (95% CI, 21-36), including one complete response.

“The data demonstrate that pembrolizumab provided meaningful improvements in survival versus the current standard of care in patients whose tumours express high levels of PD-L1,” said Dr. Luis Paz-Ares, chair of the medical oncology department, Hospital Universitario Doce de Octubre, Madrid, Spain. “These findings supporting the approval also provide further rationale for biomarker testing in order to identify those patients more likely to benefit the most from treatment with KEYTRUDA.”

Source: BusinessWire